E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002556 |
E.1.2 | Term | Ankylosing spondylitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the: • Efficacy of treatment with TCZ 4 mg/kg and 8 mg/kg versus placebo in AS patients who are naïve to treatment with TNF antagonist therapy with regard to the proportion of patients who achieve an ASAS20 response at week 12 (confirmation at week 24) • Safety of TCZ 4 mg/kg and 8 mg/kg versus placebo with regard to AEs and laboratory assessments |
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E.2.2 | Secondary objectives of the trial |
To assess the: • Efficacy of treatment with regard to radiographic benefit and improvement of physical function over 104 weeks • Long term safety and efficacy of TCZ in patients with AS • Pharmacokinetics and pharmacodynamics of TCZ in patients with AS • Immunogenicity of TCZ in patients with AS |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An intensive PK-PD sub-study will take place at selected study sites in Part 1: • PK-PD samples will be collected in a subset of approximately 30 patients, 15 from each treatment group following the first infusion. An intensive PK sub-study will take place at selected study sites in Part 2: • PK samples will be collected in a subset of approximately 45 patients, 15 patients from each treatment group following the infusion at Week 12
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E.3 | Principal inclusion criteria |
adult patients, >/=18 years of age
diagnosis of definite ankylosing spondylitis, defined by modified New York criteria, ≥ 3 months prior to baseline
active disease defined as BASDAI score of ≥ 4.0 and spinal pain assessment score of ≥40, on a 0-100 mm Visual Analogue Scale (VAS), at screening and baseline
inadequate response or intolerant to 1 or more current or previous NSAIDs
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E.4 | Principal exclusion criteria |
previous treatment with tocilizumab
previous treatment with TNF antagonist therapy
inflammatory rheumatic disease other than AS (psoriatic arthritis is allowed if patient also has definite AS as defined in inclusion criteria)
active, acute uveitis at baseline
major surgery (including joint surgery) within eight weeks prior to screening or planned major surgery within six month after randomisation
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in part 1 and part 2 is the proportion of patients with an ASAS 20 response at week 12. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
biomarker bone analysis; exploratory biomarkers (DNA and non-DNS); immunogenicity testing |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
This study will be conducted in 2 Parts followed by a common open-label extension phase. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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see protocol section 3.1.3 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |